Problem to be Solved: Cystic fibrosis (CF) is a global health issue that affects over 70,000 people worldwide, including ~30,000 Americans. Lung disease, is the primary cause of morbidity and mortality in CF patients, and is characterized by intense inflammatory responses in the airways. The Product and Long-Term Goal: Nanometics LLC (dba PHD Biosciences) (PHD) is developing a targeted small molecule enzyme inhibitor as a therapeutic for inflammation in CF lung disease. It is anticipated that this new approach will be useful to mitigate inflammation in the airways of patients. The Technological Innovation: The PHD approach is unique to all other CF therapeutics, utilizing a targeted enzyme inhibitor with high specificity and picomolar affinity to block recycling of an endogenous metabolite. Metabolite accumulation leads to robust and sustained anti-inflammatory activity. Phase I Hypotheses: This Phase I SBIR will demonstrate the feasibility of the PHD enzyme inhibitor as an oral therapeutic in Scnn1b-Tg mouse models of CF lung disease. The hypotheses tested during Phase I SBIR experiments will be: (1) a single oral dose will ameliorate inflammation for ? 24 h; and (2) once daily oral doses of the therapeutic are non-toxic and will promote a continued anti-inflammatory state. Specific Aims: Specific Aim #1. Demonstrate the Pharmacological and Concentration Dependent Effects of Oral Doses of MTDIA in the Scnn1b-Tg Mouse. Phase II: Phase II SBIR studies will further establish the mechanism of action and toxicity profile. Commercial Application: The PHD approach is a unique approach to anti-inflammatory therapy that will provide an extended benefit to patients as a single agent or part of a combinatorial approach. The current CF drug market is predicted to reach $3.9 billion by 2019.